Merkel Cell Carcinoma in Birt-Hogg-Dubé Syndrome: New Case Study

A new case report has described something doctors at the NIH (US) haven’t seen before: a person living with Birt-Hogg-Dubé Syndrome (BHD) who also developed Merkel cell carcinoma (MCC), a rare and aggressive type of skin cancer. While this might sound worrying, the important message is that this appears to be a very unusual event, and researchers found no clear evidence that BHD directly causes MCC. Still, understanding this case helps the medical community learn more about both conditions and how to better support patients.

What happened in this case?

A 58-year-old man with confirmed BHD went to his doctor after noticing a painful pink bump on his forearm that had appeared over about 10 days. People with BHD often have small, harmless skin bumps called fibrofolliculomas on the face, neck, and upper body, and this patient had many of them, something clearly shown in the clinical photos in the report.

Because the new bump looked different, his medical team performed a biopsy. The sample showed features of Merkel cell carcinoma, a fast-growing skin cancer caused either by sun-damage to DNA or by a virus called Merkel cell polyomavirus. In this case, the cancer tested positive for the virus.

How was it treated?

The care team moved quickly:

• The tumour was surgically removed
• A lymph node biopsy and PET/CT scan showed no early spread
• He received a skin graft after surgery
• He then had targeted radiation treatment to the area

A few months later, scans showed the cancer had returned in a lymph node. The patient was treated with immunotherapy, which helps the immune system recognise and attack cancer cells. Although he experienced some serious side effects (including thyroid inflammation, hepatitis, and type 1 diabetes), the treatment worked. Follow-up scans and blood tests showed no evidence of cancer, and more than two years later, he remains in complete remission.

Is MCC related to BHD?

Because this is the first reported case of MCC in someone with BHD at the NIH, the researchers carefully studied the patient’s tumour to look for a connection.

Here’s what they found:

• The patient did carry the known BHD-causing change in the FLCN gene, which is expected.
• The Merkel cell tumour did not show the usual “second hit” mutation or loss of the remaining FLCN gene—something normally required for BHD-related cancers like kidney tumours.
• The tumour contained changes typical of virus-positive MCC, not BHD-related tumour biology.

In simple terms, the cancer behaved like a typical Merkel cell carcinoma, not like a tumour caused by BHD.

The authors conclude that there is no evidence that BHD increases the risk of MCC, although more research is always helpful when something this rare appears.

What does this mean for people living with BHD?

This case reinforces a few key points:

• BHD most commonly affects the skin with fibrofolliculomas, the lungs with cysts, and the kidneys with tumours.
• Merkel cell carcinoma is not known to be part of BHD.
• Because this is only a single case, it does not change current guidance or risk expectations.
• It does, however, highlight the importance of paying attention to new or changing skin lesions and having them checked promptly—something recommended for everyone, not just people with BHD.

It also shows the value of genetic research: analysing the tumour helped determine that this was likely a coincidence rather than a new link between two rare conditions.

A hopeful outcome

Despite MCC being an aggressive cancer, this patient responded well to treatment and continues to show no evidence of disease more than two years later. His case adds to medical knowledge and reassures clinicians that, even when two rare conditions appear together, they may not necessarily be connected.

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